Comorbidities in women living with HIV: A systematic review

OBJECTIVES: Effective antiretroviral therapy (ART) has improved the life expectancy of women living with HIV (WLWH). This population is now experiencing age-related comorbidities. This systematic review presents the current understanding of the prevalence and impact of comorbidities in WLWH in the modern ART era. METHODS: MEDLINE and Embase were searched for studies (1 January 2010 to 1 September 2020) reporting the prevalence of cardiovascular, bone, renal and neurocognitive disease in WLWH aged > 18 years. Studies were included if at least 100 participants (or > 50%) were female and data analysis included prevalence by sex. RESULTS: In all, 3050 articles were identified and screened; 153 full-text articles were assessed for eligibility and 38 were included in the final review. Significant gaps in the literature were identified, notably a lack of data on WLWH aged > 50 years. The data suggest a high burden of cardiovascular, bone, renal and neurocognitive disease in WLWH compared with HIV negative women. Traditional risk factors, such as hypertension, diabetes and dyslipidaemia, were common and often poorly managed. Generalizability of the results was limited, as many studies were conducted in the USA. Comparisons between WLWH and men with HIV were limited by marked differences in demographic and socioeconomic factors. CONCLUSIONS: Women living with HIV experience a high burden of comorbid disease. Traditional risk factors are common and often poorly managed. This review also highlights the magnitude of differences between women and men living with HIV beyond the pathophysiological. Future research must unpick the complex drivers of morbidity in WLWH, to improve the holistic management of this population

A longitudinal study assessing depression in hepatitis C: does gender play a role in the new onset depression during interferon-alpha treatment?

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Protocol for a phase IV, open-label feasibility study investigating non-invasive markers of hepatic fibrosis in people living with HIV-1 and non-alcoholic fatty liver disease randomised to receiving optimised background therapy (OBT) plus maraviroc or OBT alone

Introduction At least 30% of people living with HIV (PLWH) infection have non-alcoholic fatty liver disease (NAFLD), which has now become a leading cause of hepatic fibrosis and cirrhosis. Management is based largely on lifestyle modifications, which are difficult to achieve, and therapeutic options are urgently needed. Maraviroc (MVC), through antagonism of CCR5 receptors, may reduce hepatic fibrosis progression and could be an effective treatment for NAFLD. However, dosing is usually two times per day, unlike most currently recommended antiretroviral therapies. This study will investigate the feasibility and acceptability of addition of MVC to combination antiretroviral therapy in PLWH and NAFLD as a treatment for NAFLD. Methods and analysis This is a phase IV, randomised, open-label, non-invasive feasibility study. Sixty individuals with well-controlled HIV-1 and NAFLD will be recruited from UK HIV clinics and randomised 1:1 to receive either optimised background therapy (OBT) plus MVC or OBT alone. Follow-up will be every 24 weeks for 96 weeks. The primary outcome measures will include recruitment and retention rates, adverse events and adherence. Secondary outcomes will include changes in markers of hepatic fibrosis, including the Enhanced Liver Fibrosis score, median liver stiffness measurement and controlled attenuation parameter scores on Fibroscan, and quality of life assessments. Analyses will be performed according to intention-to-treat principles. For secondary outcomes, estimated differences and 95% CIs between the groups using a t-method will be presented for continuous variables and as exact 95% binomial CIs for categorical variables. Ethics and dissemination Ethical approval was obtained through the London Dulwich UK Research Ethics Committee (reference 17/LO/2093). Results will be disseminated both through community groups and peer-reviewed scientific literature

Gender and ethnicity intersect to reduce participation at a large European hybrid HIV conference.

OBJECTIVE To evaluate how gender and ethnicity of panel members intersect to effect audience participation at a large European hybrid conference. DESIGN An observational cross-sectional study design was used to collect data at the conference and descriptive survey was used to collect data retrospectively from the participants. SETTING European AIDS Clinical Society 18th Conference; a 3223-delegate, hybrid conference held online and in London over 4 days in October 2021. MAIN OUTCOME MEASURES We observed the number and type of questions asked at 12 of 69 sessions and described characteristics of the panel composition by ethnicity, gender and seniority. A postconference survey of conference attendees collated demographic information, number of questions asked during the conference and the reasons for not asking questions. RESULTS Men asked the most questions and were more likely to ask multiple questions in the observed sessions (61.5%). People from white ethnic groups asked >95% of the questions in the observed sessions. The fewest questions were asked in the sessions with the least diverse panels in terms of both ethnicity and gender. Barriers to asking questions differed between genders and ethnicities. CONCLUSIONS Our study aims to provide evidence to help conference organisers improve leadership, equality, diversity and inclusion in the professional medical conference setting. This will support equitable dissemination of knowledge and improve education and engagement of delegates. To our knowledge, this is the first study describing conference participation by both ethnicity and gender in panellists and delegates within a hybrid conference setting

Nanoflow-nanospray mass spectrometry metabolomics reveals disruption of the urinary metabolite profiles of HIV-positive patients on combination antiretroviral therapy

Background: The use of combination antiretroviral therapy (cART) has substantially improved the outlook for patients with HIV infection. However, lifelong exposure to cART is also associated with adverse metabolic changes and an enhanced risk of renal, hepatic and cardiovascular dysfunction. This study investigated disruptions of the urinary metabolome of cART-exposed patients, thereby furthering our understanding of some of the side effects of pharmaceutical intervention. Methods: HIV-positive patients were recruited from an HIV clinic and divided into cART-naive and cART-exposed groups. HIV-negative patients were recruited from a sexual health clinic. All 89 subjects were white males. Targeted biochemistry analyses were performed on plasma samples. Urine samples were collected following an overnight fast and analysed with a highly sensitive untargeted metabolomic method using nanoflow/nanospray liquid chromatography-time of flight mass spectrometry. Datasets were analysed using projection modelling to detect metabolite markers of cART exposure. Results: Metabolites or parent compounds of all cART drugs were detected in urine extracts of all but one of the cART-exposed patients confirming adherence to the pharmaceutical regimen. Analysis of urine samples from patients on cART revealed significant reductions in selected bile acids, lipid, nucleoside and androgen metabolites. However, plasma concentrations of free or conjugated testosterone were unchanged indicating possible disruption of androgen transport or excretion in urine of patients on cART. Conclusions: Discovery-based metabolomics reveals the potential to identify novel markers of cART intervention and metabolite disruption in HIV-positive patients, which may enable the efficacy, compliance and side effects of these pharmaceutical mixtures to be investigated

PET brain imaging in HIV-associated neurocognitive disorders (HAND) in the era of combination antiretroviral therapy

Effective combination antiretroviral therapy (cART) has lead to a significant reduction in the prevalence and incidence of central nervous system (CNS) HIV-associated brain disease, particularly CNS opportunistic infections and HIV encephalitis. Despite this, cognitive deficits in people living with HIV, also known as HIV-associated neurocognitive disorders (HAND) have become more prevalent in recent years. The pathogenesis of HAND is likely to be multifactorial, however recent evidence suggests that brain microglial activation is the most likely pathogenic mechanism. Recent developments in positron emission tomography (PET) brain neuroimaging using novel brain radioligands targeting a variety of physiological changes in the brains of HIV-positive individuals have improved our understanding of the mechanisms associated with the development of HAND. This review will highlight recent PET brain neuroimaging studies in the cART era, focusing on physiological and neurochemical changes associated with HAND in people living with HIV

Transmission of hepatitis C virus in HIV‐positive and PrEP‐using MSM in England

We sought to characterize risk factors and patterns of HCV transmission amongst men who have sex with men (MSM). MSM with recently acquired HCV (AHCV) were prospectively recruited ('clinic cohort') between January and September 2017. Clinical data and risk behaviours were identified and blood obtained for HCV whole genome sequencing. Phylogenetic analyses were performed, using sequences from this cohort and two other AHCV cohorts, to identify transmission clusters. Sixteen (40.0%) men in the clinic cohort were HIV‐negative MSM. HIV‐negative MSM were younger than HIV‐positive MSM; most (81.3%) had taken HIV PrEP in the preceding year. Eighteen men (45.0%) reported injection drug use; most (34, 85.0%) reported noninjection drug use in the last year. Most in both groups reported condomless anal sex, fisting and sex in a group environment. Few (7, 17.5%) men thought partners may have had HCV. There were 52 sequences in the HCV genotype 1a phylogeny, 18 from the clinic cohort and 34 from other AHCV cohorts; 47 (90.4%) clustered with ≥1 other sequence. There were 7 clusters of 2‐27 sequences; 6 clusters contained HIV‐negative and HIV‐positive MSM and 1 cluster only HIV‐positive MSM. Four of these clusters were part of larger clusters first described in 2007. PrEP‐using MSM are at risk of HCV, sharing similar risk factors to HIV‐positive MSM. Phylogenetics highlights that PrEP‐using and HIV‐positive MSM are involved in the same HCV transmission networks. Few men demonstrated HCV awareness and risk reduction strategies should be expanded

Etravirine pharmacokinetics in HIV-infected pregnant women

__Background__ The study goal was to describe etravirine pharmacokinetics during pregnancy and postpartum in HIV-infected women. __Methods__ IMPAACT P1026s and PANNA are on-going, non-randomized, open-label, parallel-group, multi-center phase-IV prospective studies in HIV-infected pregnant women. Intensive steady-state 12-h pharmacokinetic profiles were performed from 2nd trimester through postpartum. Etravirine was measured at two labs using validated ultra performance liquid chromatography (detection limits: 0.020 and 0.026 mcg/mL). __Results__ Fifteen women took etravirine 200 mg twice-daily. Etravirine AUC0-12 was higher in the 3rd trimester compared to paired postpartum data by 34% (median 8.3 vs. 5.3 mcg*h/mL, p = 0.068). Etravirine apparent oral clearance was significantly lower in the 3rd trimester of pregnancy compared to paired postpartum data by 52% (median 24 vs. 38 L/h, p = 0.025). The median ratio of cord blood to maternal plasma concentration at delivery was 0.52 (range: 0.19-4.25) and no perinatal transmission occurred. __Conclusion__ Etravirine apparent oral clearance is reduced and exposure increased during the third trimester of pregnancy. Based on prior dose-ranging and safety data, no dose adjustment is necessary for maternal health but the effects of etravirine in utero are unknown. Maternal health and infant outcomes should be closely monitored until further infant safety data are available. __Clinical Trial registration:__ The IMPAACT protocol P1026s and PANNA study are registered at ClinicalTrials.gov under NCT00042289 and NCT00825929

Screening and prevention of HPV-related anogenital cancers in women living with HIV in Europe: Results from a systematic review.

BACKGROUND Women living with HIV (WLWH) are at increased risk of human papillomavirus (HPV)-related cancers. Throughout Europe, there is great heterogeneity among guidelines for screening programmes, access to HPV testing and HPV vaccination. The aim of this systematic review is to summarize available data on screening and prevention measures for HPV-related anogenital cancers in WLWH across the WHO European Region (WER). METHODS The systematic review followed the PRISMA guidelines and was registered on Prospero. PubMed, Embase and Web of Science databases were searched to identify available studies, written in English and published between 2011 and 2022. A metanalysis was conducted using random-effects models to calculate pooled prevalence of HPV. Subgroup analyses were conducted according to country and HPV testing. RESULTS Thirty-four articles involving 10 336 WLWH met the inclusion criteria. Studies were heterogenous in their methodology and presentation of results: 73.5% of studies focused on cervical cancer prevention, and only 4.4% on anal cancer; 76.5% of studies conducted HPV testing as a routine part of screening. The prevalence of high-risk HPV was 30.5-33.9% depending on the detection method used. A total of 77% of WLWH had cervical cytology results reported. Six studies reported the positive association of CD4 cell count <200 cells/μL with HPV prevalence and cervical abnormalities. Anal HPV testing was conducted in <8% of participants. HPV vaccination was completed in 5.6% of women (106/1902) with known vaccination status. There was no information about the vaccination status of the majority of women in the analysed studies (8434/10336). CONCLUSION Data about screening of HPV-related anogenital cancer in WLWH in Europe are heterogenous and lacking, especially in relation to anal cancer. HPV DNA testing is not routinely done as part of screening for HPV-related cancer; guidelines should include indications for when to use this test. Low CD4 count is a risk factor for HPV infection and cytological abnormalities. HPV vaccination data are poor and, when available, vaccination rates are very low among WLWH in Europe. This review concludes that significant improvements are required for data and also consistency on guidelines for HPV screening, prevention and vaccination in WLWH